Scaffolds having radiopaque markers

ABSTRACT

A scaffold includes a radiopaque marker connected to a strut. The marker is retained within the strut by one or more of a mechanical interference fit, a polymer coating or melt, and/or by friction. The marker can take the form of a bead, rivet or snap-in marker, or a tube deformed when attached to the strut. The strut is made from a tube. The strut has a thickness of about 100 microns.

BACKGROUND OF THE INVENTION Field of the Invention

The present invention relates to bioresorbable scaffolds; moreparticularly, this invention relates to bioresorbable scaffolds fortreating an anatomical lumen of the body.

Description of the State of the Art

Radially expandable endoprostheses are artificial devices adapted to beimplanted in an anatomical lumen. An “anatomical lumen” refers to acavity, or duct, of a tubular organ such as a blood vessel, urinarytract, and bile duct. Stents are examples of endoprostheses that aregenerally cylindrical in shape and function to hold open and sometimesexpand a segment of an anatomical lumen. Stents are often used in thetreatment of atherosclerotic stenosis in blood vessels. “Stenosis”refers to a narrowing or constriction of the diameter of a bodilypassage or orifice. In such treatments, stents reinforce the walls ofthe blood vessel and prevent restenosis following angioplasty in thevascular system. “Restenosis” refers to the reoccurrence of stenosis ina blood vessel or heart valve after it has been treated (as by balloonangioplasty, stenting, or valvuloplasty) with apparent success.

The treatment of a diseased site or lesion with a stent involves bothdelivery and deployment of the stent. “Delivery” refers to introducingand transporting the stent through an anatomical lumen to a desiredtreatment site, such as a lesion. “Deployment” corresponds to expansionof the stent within the lumen at the treatment region. Delivery anddeployment of a stent are accomplished by positioning the stent aboutone end of a catheter, inserting the end of the catheter through theskin into the anatomical lumen, advancing the catheter in the anatomicallumen to a desired treatment location, expanding the stent at thetreatment location, and removing the catheter from the lumen.

The following terminology is used. When reference is made to a “stent”,this term will refer to a permanent structure, usually comprised of ametal or metal alloy, generally speaking, while a scaffold will refer toa structure comprising a bioresorbable polymer, or other resorbablematerial such as an erodible metal, and capable of radially supporting avessel for a limited period of time, e.g., 3, 6 or 12 months followingimplantation. It is understood, however, that the art sometimes uses theterm “stent” when referring to either type of structure.

Scaffolds and stents traditionally fall into two generalcategories—balloon expanded and self-expanding. The later type expands(at least partially) to a deployed or expanded state within a vesselwhen a radial restraint is removed, while the former relies on anexternally-applied force to configure it from a crimped or stowed stateto the deployed or expanded state.

Self-expanding stents are designed to expand significantly when a radialrestraint is removed such that a balloon is often not needed to deploythe stent. Self-expanding stents do not undergo, or undergo relativelyno plastic or inelastic deformation when stowed in a sheath or expandedwithin a lumen (with or without an assisting balloon). Balloon expandedstents or scaffolds, by contrast, undergo a significant plastic orinelastic deformation when both crimped and later deployed by a balloon.

In the case of a balloon expandable stent, the stent is mounted about aballoon portion of a balloon catheter. The stent is compressed orcrimped onto the balloon. Crimping may be achieved by use of aniris-type or other form of crimper, such as the crimping machinedisclosed and illustrated in US 2012/0042501. A significant amount ofplastic or inelastic deformation occurs both when the balloon expandablestent or scaffold is crimped and later deployed by a balloon. At thetreatment site within the lumen, the stent is expanded by inflating theballoon.

The stent must be able to satisfy a number of basic, functionalrequirements. The stent (or scaffold) must be capable of sustainingradial compressive forces as it supports walls of a vessel. Therefore, astent must possess adequate radial strength. After deployment, the stentmust adequately maintain its size and shape throughout its service lifedespite the various forces that may come to bear on it. In particular,the stent must adequately maintain a vessel at a prescribed diameter fora desired treatment time despite these forces. The treatment time maycorrespond to the time required for the vessel walls to remodel, afterwhich the stent is no longer needed.

Examples of bioresorbable polymer scaffolds include those described inU.S. Pat. No. 8,002,817 to Limon, U.S. Pat. No. 8,303,644 to Lord, andU.S. Pat. No. 8,388,673 to Yang. FIG. 1 shows a distal region of abioresorbable polymer scaffold designed for delivery through anatomicallumen using a catheter and plastically expanded using a balloon. Thescaffold has a cylindrical shape having a central axis 2 and includes apattern of interconnecting structural elements, which will be called bararms or struts 4. Axis 2 extends through the center of the cylindricalshape formed by the struts 4. The stresses involved during compressionand deployment are generally distributed throughout the struts 4 but arefocused at the bending elements, crowns or strut junctions. Struts 4include a series of ring struts 6 that are connected to each other atcrowns 8. Ring struts 6 and crowns 8 form sinusoidal rings 5. Rings 5are arranged longitudinally and centered on an axis 2. Struts 4 alsoinclude link struts 9 that connect rings 5 to each other. Rings 5 andlink struts 9 collectively form a tubular scaffold 10 having axis 2represent a bore or longitudinal axis of the scaffold 10. Ring 5 d islocated at a distal end of the scaffold. Crown 8 form smaller angleswhen the scaffold 10 is crimped to a balloon and larger angles whenplastically expanded by the balloon. After deployment, the scaffold issubjected to static and cyclic compressive loads from surroundingtissue. Rings 5 are configured to maintain the scaffold's radiallyexpanded state after deployment.

Scaffolds may be made from a biodegradable, bioabsorbable,bioresorbable, or bioerodable polymer. The terms biodegradable,bioabsorbable, bioresorbable, biosoluble or bioerodable refer to theproperty of a material or stent to degrade, absorb, resorb, or erodeaway from an implant site. Scaffolds may also be constructed ofbioerodible metals and alloys. The scaffold, as opposed to a durablemetal stent, is intended to remain in the body for only a limited periodof time. In many treatment applications, the presence of a stent in abody may be necessary for a limited period of time until its intendedfunction of, for example, maintaining vascular patency and/or drugdelivery is accomplished. Moreover, it has been shown that biodegradablescaffolds allow for improved healing of the anatomical lumen as comparedto metal stents, which may lead to a reduced incidence of late stagethrombosis. In these cases, there is a desire to treat a vessel using apolymer scaffold, in particular a bioabsorable or bioresorbable polymerscaffold, as opposed to a metal stent, so that the prosthesis's presencein the vessel is temporary.

Polymeric materials considered for use as a polymeric scaffold, e.g.poly(L-lactide) (“PLLA”), poly(D,L-lactide-co-glycolide) (“PLGA”),poly(D-lactide-co-glycolide) or poly(L-lactide-co-D-lactide)(“PLLA-co-PDLA”) with less than 10% D-lactide,poly(L-lactide-co-caprolactone), poly(caprolactone), PLLD/PDLA stereocomplex, and blends of the aforementioned polymers may be described,through comparison with a metallic material used to form a stent, insome of the following ways. Polymeric materials typically possess alower strength to volume ratio compared to metals, which means morematerial is needed to provide an equivalent mechanical property.Therefore, struts must be made thicker and wider to have the requiredstrength for a stent to support lumen walls at a desired radius. Thescaffold made from such polymers also tends to be brittle or havelimited fracture toughness. The anisotropic and rate-dependent inelasticproperties (i.e., strength/stiffness of the material varies dependingupon the rate at which the material is deformed, in addition to thetemperature, degree of hydration, thermal history) inherent in thematerial, only compound this complexity in working with a polymer,particularly, bioresorbable polymers such as PLLA or PLGA.

One additional challenge with using a bioresorbable polymer (andpolymers generally composed of carbon, hydrogen, oxygen, and nitrogen)for a scaffold structure is that the material is radiolucent with noradiopacity. Bioresorbable polymers tend to have x-ray absorptionsimilar to body tissue. A known way to address the problem is to attachradiopaque markers to structural elements of the scaffold, such as astrut, bar arm or link. For example, FIG. 1 shows a link element 9 dconnecting a distal end ring 5 d to an adjacent ring 5. The link element9 d has a pair of holes. Each of the holes holds a radiopaque marker 11.There are challenges to the use of the markers 11 with the scaffold 10.

There needs to be a reliable way of attaching the markers 11 to the linkelement 9 d so that the markers 11 will not separate from the scaffoldduring a processing step like crimping the scaffold to a balloon or whenthe scaffold is balloon-expanded from the crimped state. These twoevents—crimping and balloon expansion—are particularly problematic formarker adherence to the scaffold because both events induce significantplastic deformation in the scaffold body. If this deformation causessignificant out of plane or irregular deformation of struts supporting,or near to markers the marker can dislodge (e.g., if the strut holdingthe marker is twisted or bent during crimping the marker can fall out ofits hole). A scaffold with radiopaque markers and methods for attachingthe marker to a scaffold body is discussed in US20070156230.

There is a continuing need to improve upon the reliability of radiopaquemarker securement to a scaffold; and there is also a need to improveupon methods of attaching radiopaque markers to meet demands forscaffold patterns or structure that render prior methods of markerattachment in adequate or unreliable.

SUMMARY OF THE INVENTION

What is disclosed are scaffolds having radiopaque markers and methodsfor attaching radiopaque markers to a strut, link or bar arm of apolymeric scaffold.

According to one aspect markers are re-shaped to facilitate a betterretention within a marker hole. Examples include a marker shaped as atube or rivet.

According to another aspect a hole for retaining the marker is re-shapedto better secure the marker in the hole. Examples include holes havingpolygonal shapes or holes having grooves.

According to another aspect of the invention a scaffold structure forholding a marker and method for making the same addresses a need tomaintain a low profile for struts exposed in the bloodstream, whileensuring the marker will be securely held in the strut. Low profiles forstruts mean thinner struts or thinner portions of struts. The desire forlow profiles addresses the degree thrombogenicity of the scaffold, whichcan be influenced by a strut thickness overall and/or protrusion from astrut surface. Blood compatibility, also known as hemocompatibility orthromboresistance, is a desired property for scaffolds and stents. Theadverse event of scaffold thrombosis, while a very low frequency event,carries with it a high incidence of morbidity and mortality. To mitigatethe risk of thrombosis, dual anti-platelet therapy is administered withall coronary scaffold and stent implantation. This is to reduce thrombusformation due to the procedure, vessel injury, and the implant itself.Scaffolds and stents are foreign bodies and they all have some degree ofthrombogenicity. The thrombogenicity of a scaffold refers to itspropensity to form thrombus and this is due to several factors,including strut thickness, strut width, strut shape, total scaffoldsurface area, scaffold pattern, scaffold length, scaffold diameter,surface roughness and surface chemistry. Some of these factors areinterrelated. Low strut profile also leads to less neointimalproliferation as the neointima will proliferate to the degree necessaryto cover the strut. As such coverage is a necessary step to completehealing. Thinner struts are believed to endothelialize and heal morerapidly.

Markers attached to a scaffold having thinner struts, however, may nothold as reliably as a scaffold having thicker struts since there is lesssurface contact area between the strut and marker. Embodiments ofinvention address this need. According to another aspect a thickness ofthe marker and strut is kept below threshold values while reliablyretaining the marker in the hole.

According to other aspects of the invention, there is a scaffold,medical device, method for making such a scaffold, method of attaching amarker to a strut or bar arm of a scaffold, or method for assembly of amedical device comprising such a scaffold having one or more, or anycombination of the following things (1) through (19):

-   -   (1) A method to reduce the thrombogenicity, or a scaffold having        reduced thrombogenicity, the scaffold comprising a strut, the        strut including a strut thickness and a marker attached to the        strut, wherein the strut has a thickness (t) and the marker has        a length (L, as measured from abluminal to luminal surface        portions) and is held in the strut, the marker including a        portion that can protrude outward from an abluminal and/or        luminal surface of the strut, wherein the marker length (L) and        strut/link/bar arm thickness (t) are related as follows:        1.2≤(L/t)≤1.8; 1.1≤(L′/t)≤1.5; 1.0≤(L/t)≤1.8; and/or        1.0≤(L′/t)≤1.5, where L is an undeformed length (e.g., rivet,        tube), L′ is a deformed length (e.g. a rivet, coating or snap-in        marker between abluminal and luminal surfaces).    -   (2) A scaffold comprising a bar arm, link or strut having a hole        holding a marker, or a method for making the same according to        one or more, or any combination of features described for a        Concept A through Concept G infra and with reference to        illustrative examples shown in FIGS. 3A-3C, FIGS. 4A, 4B, 5A and        5B, FIGS. 6A and 6B, FIG. 6C, FIGS. 7A-7B, FIGS. 8A-8C, FIGS.        9A-9C, FIGS. 10A-10B, FIGS. 11A-11B, FIGS. 12A-12B and FIGS.        13A-13B, respectively.    -   (3) An aspect ratio (AR) of strut width (w) to wall        thickness (t) (AR=w/t) is between 0.5 to 2.0, 0.5 to 1.5, 0.7 to        1.5, 0.7 to 1.3, 0.9 to 1.5, 0.9 to 1.2, 1.0 to 1.5, 1.5 to 2.0,        or 2.0 to 3.0;    -   (4) A scaffold comprising a strut, link and/or bar arm including        a marker secured to the strut, link and/or bar arm according to        any of Concept A, Concept B, Concept C, Concept D, Concept E,        Concept F or Concept G-type markers.    -   (5) A scaffold comprising a deformed marker secured to a strut,        bar arm and/or link, wherein the marker is a rivet, snap-fit,        irregularly-shaped, tube or spherical marker before the marker        is deformed.    -   (6) A marker having a head and a tail such as a rivet, hollow        tube, solid tube, polygonal, oblate spheroid, and/or spherical        body. The marker is secured to a strut, bar arm, link and/or        connector.    -   (7) A combined bump (luminal side plus abluminal side, and        referring to a portion of a marker and/or polymer at the marker)        is no more than a strut or link thickness, e.g., no more than        100 or 85 microns, so that the length at the marker is at most        twice a strut or bar arm thickness at the marker.    -   (8) A combined bump (luminal side plus abluminal side, and        referring to a portion of a marker and/or polymer at the marker)        is at least 10-50% more than a thickness of a strut or bar arm        at the marker.    -   (9) A wall thickness for a scaffold (pre-crimp diameter of 3 to        5 mm) is less than 150 microns, less than 140 microns, less than        130 microns, about 100 micron, 80 to 100 microns, 80 to 120        microns, 90 to 100 microns, 90 to 110 microns, 110 to 120        microns, or 95 to 105 microns. More preferably a wall thickness        is between 80 and 100 microns, and more preferably between 85        and 95 microns; and    -   (10) A wall thickness for a scaffold (pre-crimp diameter of 7 to        10 mm) is less than 280 microns, less than 260 microns, less        than 240 microns, about 190 micron, 149 to 186 microns, 149 to        220 microns, 170 to 190 microns, 170 to 210 microns, 210 to 220        microns. More preferably a wall thickness is between 150 and 190        microns for a scaffold having an outer diameter of 7, 8 or 9 mm.    -   (11) A polymeric scaffold is heated about 0-20 degrees above its        Tg during or after marker placement.    -   (12) The radiopaque marker is comprised of platinum,        platinum/iridium alloy, iridium, tantalum, palladium, tungsten,        niobium, zirconium, iron, zinc, magnesium, manganese or their        alloys.    -   (13) A method for making a medical device, comprising: providing        a polymer scaffold including a strut having a hole formed in the        strut, wherein the hole has a length and a width; and providing        a radiopaque marker having a first end, second end, and medial        portions; and attaching the marker to the scaffold including        placing the marker into the hole; wherein when the marker is        attached to the scaffold the medial portion is disposed in the        hole and the marker is retained in the hole at least partially        by one or both of the first and second ends.    -   (14) The method of (6) according to one or more, or any        combination of the following things: wherein the attaching step        includes deforming at least one of the first and second ends        such that the deformed end has a width greater than the hole        width; wherein the marker is a rivet having a head and tail, and        wherein the tail is the deformed end; wherein the rivet head is        placed on a luminal side of the strut and held in place by a        mandrel, and the tail disposed on the abluminal strut side is        deformed by a roller or pin; wherein the marker is a tube and        both the first and second ends are deformed to have a width        greater than the hole width; wherein the attaching step includes        using a tool having jaws forming points to engage the tube ends,        wherein the jaws deform the ends; wherein the marker is a        snap-fit marker; wherein the marker has an undeformed length        (L), a deformed length (L′), and the strut has a thickness (t),        and the marker lengths and strut thickness are related as        follows: 1.2≤(L/t)≤1.8; 1.1≤(L′/t)≤1.5; and/or wherein the        marker has an undeformed length (L), a deformed length (L′), and        the strut has a thickness (t), and the marker lengths and strut        thickness are related as follows: 1.0≤(L/t)≤1.8; and        1.0≤(L′/t)≤1.5.    -   (15) A method for making a medical device, comprising: providing        a polymer scaffold including a strut; making a grooved hole in        the strut including forming at least one groove in a wall of the        hole; and attaching a radiopaque marker to the scaffold        including placing the marker into the grooved hole.    -   (16) The method of (8) according to one or more, or any        combination of the following things: wherein the grooved hole        has vertical grooves extending generally parallel to a bore axis        of the hole; wherein the grooved hole has one or more spiral        grooves; wherein the grooved hole is a tapped hole having        between about 2 to 6 threads per 100 microns; wherein the        grooved hole is an annular hole disposed between upper and lower        rims of the hole; wherein the making the grooved hole includes        using a laser and reflector to etch the annular hole; wherein        the hole is polygonal hole; wherein the hole elliptical; further        comprising applying a polymer melt or coating to the hole and        marker, whereby the polymer becomes disposed between gaps        between the at least one groove and marker.    -   (17) A method, comprising: providing a scaffold made from a        polymer tube, the scaffold having a network of elements        including a strut; providing a hole in the strut or link,        wherein the hole extends from an abluminal surface to a luminal        surface of the strut; disposing a radiopaque marker at least        partially within the hole; and applying a coating comprising a        polymer to the luminal and abluminal surfaces; wherein a        thickness measured between abluminal and luminal surfaces of the        coating nearby to the marker (tc) is related to a length (L)        measured between abluminal and luminal surfaces of the coating        at the marker as 0.8≤(L/tc)≤1.8.    -   (18) The method of (10) according to one or more, or any        combination of the following things: wherein t is about 100        microns; and/or wherein the marker height (L), the marker is        secured to a strut, the strut thickness is t, and 1.1≤(L/t)≤1.5.    -   (19) A medical device, comprising: a scaffold made from a        polymer tube, the scaffold having a network of elements        including a strut or link; a hole formed in the strut or link,        wherein the hole extends from the abluminal surface to the        luminal surface; a radiopaque marker at least partially disposed        within the hole; and a coating comprising a polymer on the        luminal and abluminal surfaces; wherein a thickness measured        between abluminal and luminal surfaces of the coating adjacent        the marker (tc) is related to a length (L) measured between        abluminal and luminal surfaces of the coating at the marker as        1.1≤(L/tc)≤1.5.

INCORPORATION BY REFERENCE

All publications and patent applications mentioned in the presentspecification are herein incorporated by reference to the same extent asif each individual publication or patent application was specificallyand individually indicated to be incorporated by reference. To theextent there are any inconsistent usages of words and/or phrases betweenan incorporated publication or patent and the present specification,these words and/or phrases will have a meaning that is consistent withthe manner in which they are used in the present specification.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of a portion of a prior art scaffold. Thescaffold is shown in a crimped state (balloon not shown).

FIG. 2 is a top partial view of a scaffold showing a link connectingadjacent rings. The link includes holes for holding markers.

FIG. 2A is a partial side-cross sectional view of the link of FIG. 2taken at section IIA-IIA with a spherical marker being placed in thehole.

FIG. 2B shows the link of FIG. 2A after the marker is placed in thehole.

FIG. 3A shows a first embodiment of sealing layers of a polymer appliedto abluminal and luminal surfaces of a marker strut.

FIG. 3B shows a second embodiment of sealing layers of a polymer appliedto abluminal and luminal surfaces of a marker strut.

FIG. 3C shows a third embodiment of sealing layers of a polymer appliedto abluminal and luminal surfaces of a marker strut.

FIG. 4A is a top view of a polygonal, four-sided marker hole without aninserted marker.

FIG. 4B is a top view of the polygonal, four-sided marker hole of FIG.4A with an inserted marker.

FIG. 5A is a top view of a polygonal, six-sided marker hole without aninserted marker.

FIG. 5B is a top view of the polygonal, six-sided marker hole of FIG. 5Awith an inserted marker.

FIG. 6A is a top view of a marker hole with grooves, without an insertedmarker.

FIG. 6B is a top view of the marker hole of FIG. 6A, with an insertedmarker.

FIG. 6C is a side cross-sectional view of a link with marker hole havinggrooves according to another embodiment.

FIG. 7A is a cross sectional view of the marker according to any of theembodiments of FIGS. 4A, 4B, 5A and 5B, where FIG. 7A shows the markerhole and marker without a polymer coating.

FIG. 7B is a cross sectional view of the marker according to any of theembodiments of FIGS. 4A, 4B, 5A and 5B, where FIG. 7B shows the markerhole and marker with a polymer coating.

FIG. 8A is a partial side-cross sectional view of a link according toanother embodiment. A spherical marker is being placed in a hole of thelink.

FIG. 8B shows the link of FIG. 8A after the marker is placed in thehole.

FIG. 8C shows a method for making the hole of FIG. 8A.

FIGS. 9A and 9B show a side and top view, respectively, of a markeraccording to another embodiment.

FIG. 9C is a cross-sectional view of a link having a hole and the markerof FIG. 9A embedded in the hole.

FIGS. 10A and 10B are cross-sectional views of a link and marker andmethod of attaching the marker to the link according to anotherembodiment.

FIGS. 11A and 11B are cross-sectional views of a link and marker andmethod of attaching the marker to the link according to anotherembodiment.

FIGS. 12A and 12B are cross-sectional views of a link and marker andmethod of attaching the marker to the link according to anotherembodiment.

FIGS. 13A and 13B are cross-sectional views of a link and marker andmethod of attaching the marker to the link according to anotherembodiment.

DETAILED DESCRIPTION

In the description like reference numbers appearing in the drawings anddescription designate corresponding or like elements among the differentviews.

For purposes of this disclosure, the following terms and definitionsapply:

The terms “about,” “approximately,” “generally,” or “substantially” mean30%, 20%, 15%, 10%, 5%, 4%, 3%, 2%, 1.5%, 1%, between 1-2%, 1-3%, or0.5%-5% less or more than, less than, or more than a stated value, arange or each endpoint of a stated range, or a one-sigma, two-sigma,three-sigma variation from a stated mean or expected value (Gaussiandistribution). For example, d1 about d2 means d1 is 30%, 20%, 15%, 10%,5%, 4%, 3%, 2%, 1.5%, 1%, 0% or between 1-2%, 1-3%, 1-5%, or 0.5%-5%different from d2. If d1 is a mean value, then d2 is about d1 means d2is within a one-sigma, two-sigma, or three-sigma variance or standarddeviation from d1.

It is understood that any numerical value, range, or either rangeendpoint (including, e.g., “approximately none”, “about none”, “aboutall”, etc.) preceded by the word “about,” “approximately,” “generally,”or “substantially” in this disclosure also describes or discloses thesame numerical value, range, or either range endpoint not preceded bythe word “about,” “approximately,” “generally,” or “substantially.”

A “stent” means a permanent, durable or non-degrading structure, usuallycomprised of a non-degrading metal or metal alloy structure, generallyspeaking, while a “scaffold” means a temporary structure comprising abioresorbable or biodegradable polymer, metal, alloy or combinationthereof and capable of radially supporting a vessel for a limited periodof time, e.g., 3, 6 or 12 months following implantation. It isunderstood, however, that the art sometimes uses the term “stent” whenreferring to either type of structure.

“Inflated diameter” or “expanded diameter” refers to the inner diameteror the outer diameter the scaffold attains when its supporting balloonis inflated to expand the scaffold from its crimped configuration toimplant the scaffold within a vessel. The inflated diameter may refer toa post-dilation balloon diameter which is beyond the nominal balloondiameter, e.g., a 6.5 mm balloon (i.e., a balloon having a 6.5 mmnominal diameter when inflated to a nominal balloon pressure such as 6times atmospheric pressure) has about a 7.4 mm post-dilation diameter,or a 6.0 mm balloon has about a 6.5 mm post-dilation diameter. Thenominal to post dilation ratios for a balloon may range from 1.05 to1.15 (i.e., a post-dilation diameter may be 5% to 15% greater than anominal inflated balloon diameter). The scaffold diameter, afterattaining an inflated diameter by balloon pressure, will to some degreedecrease in diameter due to recoil effects related primarily to, any orall of, the manner in which the scaffold was fabricated and processed,the scaffold material and the scaffold design.

When reference is made to a diameter it shall mean the inner diameter orthe outer diameter, unless stated or implied otherwise given the contextof the description.

When reference is made to a scaffold strut, it also applies to a link orbar arm.

“Post-dilation diameter” (PDD) of a scaffold refers to the innerdiameter of the scaffold after being increased to its expanded diameterand the balloon removed from the patient's vasculature. The PDD accountsfor the effects of recoil. For example, an acute PDD refers to thescaffold diameter that accounts for an acute recoil in the scaffold.

A “pre-crimp diameter” means an outer diameter (OD) of a tube from whichthe scaffold was made (e.g., the scaffold is cut from a dip coated,injection molded, extruded, radially expanded, die drawn, and/orannealed tube) or the scaffold before it is crimped to a balloon.Similarly, a “crimped diameter” means the OD of the scaffold whencrimped to a balloon. The “pre-crimp diameter” can be about 2 to 2.5, 2to 2.3, 2.3, 2, 2.5, 3.0 times greater than the crimped diameter andabout 0.9, 1.0, 1.1, 1.3 and about 1-1.5 times higher than an expandeddiameter, the nominal balloon diameter, or post-dilation diameter.Crimping, for purposes of this disclosure, means a diameter reduction ofa scaffold characterized by a significant plastic deformation, i.e.,more than 10%, or more than 50% of the diameter reduction is attributedto plastic deformation, such as at a crown in the case of a stent orscaffold that has an undulating ring pattern, e.g., FIG. 1. When thescaffold is deployed or expanded by the balloon, the inflated balloonplastically deforms the scaffold from its crimped diameter. Methods forcrimping scaffolds made according to the disclosure are described inUS20130255853.

Bioresorbable scaffolds comprised of biodegradable polyester polymersare radiolucent. In order to provide for fluoroscopic visualization,radiopaque markers are placed on the scaffold. For example, the scaffolddescribed in U.S. Pat. No. 8,388,673 ('673 patent) has two platinummarkers 206 secured at each end of the scaffold 200, as shown in FIG. 2of the '673 patent.

FIG. 2 is a top planar view of a portion of a polymer scaffold, e.g., apolymer scaffold having a pattern of rings interconnected by links as inthe case of the '673 patent embodiments. There is a link strut 20extending between rings 5 d, 5 in FIG. 2. The strut 20 has formed leftand right structures or strut portions 21 b, 21 a, respectively, forholding a radiopaque marker. The markers are retainable in holes 22formed by the structures 21 a, 21 b. The surface 22 a corresponds to anabluminal surface of the scaffold. An example of a correspondingscaffold structure having the link 20 is described in FIGS. 2, 5A-5D,6A-6E and col. 9, line 3 through col. 14, line 17 of the '673 patent.The embodiments of a scaffold having a marker-holding link structure ormethod for making the same according to this disclosure in someembodiments include the embodiments of a scaffold pattern according toFIGS. 2, 5A-5D, 6A-6E and col. 9, line 3 through col. 14, line 17 of the'673 patent.

One method for marker placement forces a spherical-like body into acylindrical hole. This process is illustrated by FIGS. 2A and 2B. Shownin cross-section is the hole 22 and surrounding structure of the linkportion 21 a as seen from Section IIa-IIa in FIG. 2. The hole 22 extendsthrough the entire thickness (t) of the strut portion 21 a and the hole22 has an about constant diameter (d) from the luminal surface 22 b tothe abluminal surface 22 a. A generally spherical marker 25 is force-fitinto the hole 22 to produce the marker 25′ in the hole 22 illustrated inFIG. 2B. The spherical marker 25 has a volume about equal to, less thanor greater than the volume of the open space defined by the plane of theabluminal surface 22 a, the plane of the luminal surface 22 b and thegenerally cylindrical walls 24 of the hole 22. The spherical body isreshaped into body 25′ by the walls 24 and a tool. The deformed shape25′ may be achieved by using one or two rollers pressed against thesphere 25 when it is disposed within the hole 22. The rollers (notshown) are pressed against each side of the marker 25 to produce thedeformed marker 25′ structure shown in FIG. 2B. Alternatively, themarker 25 may be held on a tip of a magnetized, or vacuum mandrel andpressed (from the abluminal surface 22 a side) into the hole 22 while anon-compliant flat surface is pressed into the marker from the luminalside 22 b. Referring to FIG. 2B, the marker 25′ has an abluminal surface25 a that is about flush with surface 22 a and luminal surface 25 b thatis about flush with surface 22 b. Methods for placing the marker 25 inthe hole 22 are discussed in US20070156230.

According to one example, the hole 22 has a hole diameter (d) of 233.7μm and an average initial spherical marker size (Johnson-Matthey markerbeads) of 236.7 μm. The thickness (t) is 157.5 microns and hole 22volume is t×πd²=6.76E6 μm³. The average spherical volume size is 6.94E6μm³. Hence, in this embodiment when the spherical marker 25 is press-fitinto the hole 22, the marker 25 is deformed from a generally sphericalshape into more of a cylindrical shape. In some embodiments an averagevolume size for the marker 25 may be only slightly larger in volume (3%)than a hole 22 volume. Larger beads presumably stretch the marker brimwhile smaller beads will contact the walls 24 when deformed, but do notfill the hole 22 volume completely. As would be understood, the aboutflush with the luminal and abluminal surfaces accounts for the variancesin marker 25 volume size from the manufacturer and volume size variancesof the hole 22 volume.

TABLE 1 contains a theoretical volume of an average spherical platinummarker 25 relative to that of the hole 22 for a Scaffold A and aScaffold B.

TABLE 1 Marker and Hole Dimensions Strut Thickness Marker Hole AverageMarker Idealized Marker Average Marker Scaffold (μm) Diameter (μm)Diameter (μm) Hole Volume (μm³) Volume (μm³) A 157.5 233.7 236.7 6.76E66.94E6 B 100 241.3 236.7 4.57E6 6.94E6

The larger the marker volume is relative to the hole volume, the morethe marker brim or space 22 must increase in size if the marker 25′ willbe flush with the surfaces 22 a, 22 b. Otherwise, if the volume for thehole 22 does not increase marker material would be left protruding aboveand/or below the hole 22.

With respect to the different thickness struts of Scaffold A andScaffold B (TABLE 1) it will be appreciated that an acceptable marker 25fitting method and/or structure for Scaffold A (thick struts) may not beacceptable for Scaffold B (thin struts). It may be necessary to changethe volume and/or shape size of the hole and/or marker, and/or method ofattachment of the marker to a hole when a strut thickness is reduced insize, e.g., when there is an about 37% reduction in strut thickness.

There are several dimensional parameters that result in a physicalinteraction between the strut walls 24 and marker 25 surface sufficientto keep the marker in the hole 25 during scaffold manipulations, such asdrug coating, crimping and scaffold expansion. Factors (1)-(3) thataffect the physical securement of the marker 25′ in the hole 22 include:

-   -   (1) The interference fit between the marker 25′ and the inside        surface or brim 24 of the marker hole 22. This fit is a function        of        -   The total contact area between the marker 25′ and the            polymer walls or brim 24.        -   The residual stresses in the marker brim 24 polymer and 25′            that results in a compressive or hoop stress between the            marker brim 24 and marker 25′.    -   (2) The roughness of the marker 25′ surface and surface of the        brim 24, or coefficient of static friction between the        contacting marker and wall surfaces.    -   (3) Where a drug-polymer coating is applied (not shown in FIG.        2B), the gluing-in effect of the drug/polymer coating. The        contribution of this coating to marker 25′ retention comes down        to the fracture strength of the coating on the abluminal or        luminal surfaces 22 a, 22 b as the coating must fracture through        its thickness on either side for the marker 25′ to become        dislodged.

With respect to factor (3), in some embodiments an Everolimus/PDLLAcoating is applied after the marker 25′ is fit in place. This type ofcoating can seal in the marker 25. However, an Everolimus/PDLLA coatingtends to be thin (e.g., 3 microns on the abluminal surface 22 a and 1micron on the luminal surface 22 b), which limits it's out of planeshear strength resisting dislodgment of the marker from the hole.

In some embodiments a polymer strut, bar arm and/or link has a thicknessabout, or less than about 100 microns, which is less than the wallthickness for known scaffolds cut from tubes. There are severaldesirable properties or capabilities that follow from a reduction inwall thickness for a scaffold strut; for example, a reduction from theScaffold A wall thickness to Scaffold B wall thickness. The advantagesof using the reduced wall thickness include a lower profile and hencebetter deliverability, reduced acute thrombogenicity, and potentiallybetter healing. In some embodiments the Scaffold B (100 micron wallthickness) has a pattern of rings interconnected by struts as disclosedin the '673 patent.

In some embodiments it is desirable to use the same size marker 25 forScaffold B as with Scaffold A, so that there is no difference, orreduction, in radiopacity between the two scaffold types. Reducing thestrut thickness, while keeping the marker hole 22 the same size canhowever result in the marker protruding above and/or below the strutsurfaces due to the reduced hole volume. It may be desirable to keep theabluminal and luminal surfaces 25 a, 25 b of the marker 25′ flush withcorresponding surfaces 22 a, 22 b for Scaffold B, in which case the hole22 diameter (d) may be increased to partially account for the reducedhole volume resulting from the thinner strut. This is shown in TABLE 1for Scaffold B, which has a hole diameter greater than the hole diameterfor Scaffold A.

With respect to Factor (1) it will be appreciated that the substantiallyfrictional force relied on to resist dislodgement of the marker 25′ fromthe hole 22 reduces as the strut thickness is reduced. When using afixed sized marker of constant volume, and assuming the marker fills acylindrical hole, the contact area between the marker and hole sidewallmay be expressed in terms of a marker volume and strut thickness, as inEQ. 1.

A=2 (πtV)^(1/2)   (EQ. 1)

-   -   Where        -   A=Contact area between marker hole sidewall and marker        -   t=Strut thickness        -   V=marker volume

EQ. 1 shows that in a limiting case of the strut 21 a thickness becomingvery thin (t→0), the marker 25′ becomes more and more like a thin disc,which would have minimal mechanical interaction with the wall 24. Hencethe frictional forces between the marker 25′ and wall 24 decreasesbecause the contact area is reduced. Comparing Scaffold A with ScaffoldB, the marker 25′ retention force in the hole 22 therefore becomes worsedue to the about 37% reduction in strut thickness. Indeed, it may beexpected that the Factor A (frictional) forces that hold the marker 25′in the hole reduce by about 20%, which 20% reduction is the surface areareduction of the walls 24 when the strut thickness is reduced by theabout 37% (Scaffold A→Scaffold B). This assumes the coefficients ofstatic friction and level of residual hoop stress are otherwiseunchanged between Scaffold A and B.

According to another aspect of the disclosure there are embodiments of astrut having a hole for holding a radiopaque marker and methods forsecuring a marker to a strut. The embodiments address the ongoing needfor having a more secure attachment of a marker to a polymer strut. Inpreferred embodiments the polymer strut has a thickness, or a scaffoldcomprising the strut is cut from a tube having a wall thickness lessthan about 160 μm or 150 μm, a wall thickness of about 100 μm or a wallthickness less than 100 μm and while retaining the same size marker as astrut having a thickness between 150-160 μm, so that the radiopacity ofthe scaffold does not change.

An improved securement of a marker to a hole according to the disclosureincludes embodiments having one or more of the following Concepts Athrough G:

-   -   A. Following marker insertion a sealing biodegradable polymer is        applied to secure the marker in place (Concept A).    -   B. The strut hole is made in an irregular shape to increase an        adhesive and mechanical locking effect of a scaffold coating        (Concept B).    -   C. The marker has roughened surfaces to increase the coefficient        of friction between the polymer walls and marker (Concept C).    -   D. The holes are made concave to increase the contact area        and/or to provide a mechanical engagement between the marker and        the hole (Concept D).    -   E. Radiopaque markers shaped like, or usable as rivets are        attached to the hole (Concept E).    -   F. Polygonal or Irregular markers (Concept F).    -   G. Snap-in markers (Concept G).

A. Addition of a Sealing Biodegradable Polymer After Marker Insertion,but Before Drug Spray

According to Concept A, sealing layers of polymer 30 are applied to theabluminal and/or luminal surfaces 22 a, 22 b of the strut 21 a near themarker 25′ and luminal and abluminal surfaces 25 a, 25 b surfaces of themarker 25′ as shown in FIGS. 3A-3C. The amount of sealing polymer 30applied on the marker 25 may be significant but without creating anunsatisfactory bump or protrusion on the abluminal or luminal surfaces.To increase the available space for the sealing polymer (withoutreducing the marker size or creating a large bump on the surface) thehole 22 may be made wider, so that the marker 25 when pressed anddeformed into the hole 22 is recessed from the abluminal surface 22 aand/or abluminal surface 22 b. This is shown in FIGS. 3B and 3C. In FIG.3B the marker 25′ is recessed from the side 22 a but flush with 22 b. InFIG. 3C the marker 25′ is recessed on both surfaces.

The sealing polymer 30 may be applied in different ways. One approach isto apply a small amount of solution consisting of a biodegradablepolymer dissolved in solvent. This can be done with a fine needleattached to a micro-syringe pump dispenser. The solution could beapplied to both the abluminal and luminal surfaces of the marker andmarker brim portions of the hole 22 (FIGS. 3A-3C). Suitable polymersinclude poly(L-lactide) (“PLLA”), poly(D,L-lactide-co-glycolide)(“PLGA”), poly(D-lactide-co-glycolide), poly(D,L-lactide) (“PDLLA”)poly(L-lactide-co-caprolactone) (“PLLA-PCL”) and other bioresorbablepolymers. Solvents include chloroform, acetone, trichloroethylene,2-butanone, cyclopentanone, ethyl acetate, and cyclohexanone.

Alternatively, the sealing polymer may be applied in a molten state. Ascompared to the solvent application embodiment of the sealing polymer, apolymer applied in the molten state may produce a more sizable bump orprotrusion on the abluminal and/or luminal surface 22 a, 22 b. Whileavoidance of bumps on these surfaces is generally of concern, smallbumps or protrusions are acceptable if they are less than the strutthickness. For example, in some embodiments the bump is less than about100 microns, or about 85 microns (combined bumps on luminal andabluminal sides). Thus the length of the marker (L′ or L) may be up toabout 100 or 85 microns higher than the strut thickness, as in a strutthickness of about 100 or 85 microns.

B. Use of a Polygonal or Irregular Marker Hole to Improve AdhesiveEffect of Coating

According to Concept B, the marker hole 22 is modified to increase theadhesive effect of a drug/polymer coating on increasing the markerretention. If larger gaps are made between the marker 25 and wall 24 ofthe hole 22 more of the coating can become disposed between the marker25′ and wall 24 of the hole 22. The presence of the coating in this area(in addition to having coating extending over the surfaces 22 a, 25 a,22 b and 25 a) can help to secure the marker 25 in the hole because thesurface area contact among the coating, wall 24 and marker 25 isincreased. Essentially, the coating disposed within the gaps between thewall 24 and marker 25 can perform more as an adhesive. In addition, thecoating filling in around the deformed marker bead can improve retentionvia mechanical interlocking. Gaps can be made by forming the hole withrectangular, hexagonal or more generally polygonal sides as opposed to around hole. When a spherical marker 25 is pressed into a hole havingthese types of walls there will be gaps at each wall corner.

FIGS. 4A and 4B show modified marker-holding strut portions 31 a, 31 bbefore and after, respectively, a marker 25 is pressed into each hole 32of the strut portions 31 a, 31 b. The holes 32 are formed as rectangularholes. Since there are four sides 34 to a rectangular, there are fourcorners to the hole 32. As can be appreciated from FIG. 4B there arefour gaps 33 between the hole walls 34 and the bead 25′. The gaps 33 arepresent at each wall corner of the rectangular hole 32.

FIGS. 5A and 5B show modified marker-holding strut portions 41 a, 41 bbefore and after, respectively, a marker 25 is pressed into each hole 42of the strut portions 41 a, 41 b. The holes 42 are formed as hexagonalholes. Since there are six sides 44 to a hexagon, there are six cornersto the hole 42. As can be appreciated from FIG. 5B there is at least oneand up to six gaps 43 between the hole walls 44 and the marker 25′.

Referring to FIGS. 7A and 7B there is shown cross-sectional side-viewsof the holes 32 and 42 with the marker 25′ in the hole. The view of FIG.7A is taken from section VIIa-VIIa in FIGS. 4B and 5B. As shown there isthe gap 33, 43 present at the corner, which provides space for thepolymer coating 32 (FIG. 7B) to lodged when the coating is applied tothe scaffold. The coating 32 is disposed between the surface of themarker 25′ and wall 34, 44 of the hole 32, 42 combined with the coatingdisposed on the luminal and/or abluminal surfaces 32 a, 32 b, 42 a, 42b. The polymer coating 32 shown in FIG. 7B may be a drug-polymer coatingor polymer coating applied by spraying, or a molten polymer applied tothe brim of the hole 22 and over the marker 25′.

C. Roughened Wall Surfaces

FIGS. 6A and 6B show modified marker-holding strut portions 51 a, 51 bbefore and after, respectively, a marker 25′ is pressed into each hole52 of the strut portions 51 a, 51 b. The holes 52 are formed as bearclawholes or holes having grooves 54 formed through the thickness and alongthe perimeter of the hole. The grooves 54 may be formed using a laserdirected down into the hole and moved circumferentially about theperimeter to cut out the grooves 54. Each of the grooves 54 can serve asa gap that fills up with a coating or molten polymer 32 to form anadhesive binding surfaces of the marker 25′ to walls of the hole 52, inthe same way as the embodiments of FIGS. 4A, 4B, 5A and 5B where thebinding occurs at wall corners 33, 43.

Grooves may be formed as spiral grooves as opposed to grooves thatextend straight down (i.e., into the paper in FIGS. 6A-6B). Spiralgrooves may be formed by a tapping tool such as a finely threaded drillbit or screw (about 1, 2, 3, 4, 5 or 4-10 threads per 100 microns). Thisstructure is shown in FIG. 6C where a strut portion 51 a′ having anabluminal surface 52 a′ and hole 52′ is tapped to produce one or morespiral grooves surface 54′. The hole 52′ may have 2 to 10 threads per100 microns, or a groove may have a pitch of about 10, 20, 30 or 50microns.

Any combination of the Concept B and Concept C embodiments arecontemplated. A hole may be polygonal such as rectangular, square orhexagonal with the grooves formed on walls. There may be 1, 2, 3, 4,5-10, a plurality or grooves, grooves every 10, 20, 45, or 10-30 degreesabout the perimeter of the hole. “Grooves” refers to either straightgrooves (FIG. 6A-6B) or spiral grooves or threading (FIG. 6C). Thegrooves may be formed in a polygonal hole (e.g., square, rectangular,hexagonal) or elliptical hole (e.g., a circular hole).

D. Marker Having Concave walls

According to Concept D, a marker hole has a concave surface betweenupper and lower rims to hold a marker in place. Referring to FIGS.8A-8B, there is shown a strut portion 61 a having an abluminal andluminal surface 62 a, 62 b respectively and a hole 62 to receive themarker 25, as shown. The wall 64 of the hole is cylindrical, like in theFIG. 2A embodiment, except that the wall 64 includes an annular andconcave surface (or groove) formed about the perimeter. The (groove)surface 64 c located between the upper and lower edges of the hole 62 isbetween an optional upper and lower rim 64 a, 64 b of the hole 62. Therims 64 a, 64 b help retain the marker 25 in the hole 62. According tothis embodiment a hole has a pseudo-mechanical interlock featureprovided by the annular groove 64 c. Referring to FIG. 8B the deformedmarker 25′ has a portion 26 a generally taking the shape of the annulargroove 64 c having a concave shape, or displacing into the space definedby this part of the wall when the marker is forced into the hole. Therims 64 a, 64 b, and the convex shape of 25′ nested into concave annulargroove 64 c, resist dislodgment of the marker 25′ from the hole 62. Ascan be appreciated from FIG. 8B the marker 25′ would have to deformbefore it dislodges from the hole 62. Because the marker 25′ must deformto dislodge from the hole 62, the hole 62 having the annular groove 64 cbetween upper and lower rims 64 a, 64 b provides a mechanical interlock.In contrast to other embodiments, the structure shown in FIG. 8B neednot rely primarily or solely on friction and/or an adhesive/coating tosecure the marker in place.

FIG. 8C illustrates a method for making the hole 62 according to ConceptD using a laser 200 reflected off a reflective surface 204 of areflector tool or reflector 202. The reflector 202 is frustoconical andis configured to extend up through the untapped hole 20. The reflector202 is pressed and held against the luminal surface 62 b to hold it inplace. The reflective surface 204 is arranged at an angle of between 20to 60 degrees with respect to the untapped wall of the hole 20. Thesurface 204 is arranged so that laser light impacts the wall 64 c′ atabout a right angle as shown. The laser 200 is directed onto the surface204, which reflects the light towards the wall and causes the laserenergy to etch-out the groove. The laser is traced (or scanned) aboutthe perimeter of the hole 20 to make the annular groove shown in FIG.8A. The laser would trace a circle on the reflector 202, just inside theedges of the marker hole 20. The groove thickness (i.e., distancebetween the upper and lower rims 64 a, 64 b) can be up to about 60% to80% and/or between about 20% to 50% of the strut thickness.

In the embodiments, the reflectors 202 having surface 204 can have afrustoconical part for each of the paired holes (FIG. 2), or insteadhave a set of hemispheres or cones for a set of marker holes Analternative laser reflector would be one which does not protrude intothe marker bead hole but which presents a concave surface pressed upagainst the bottom of the hole with edges at surface 62 b. A laser beamimping on this surface would be reflected against the opposite wall ofhole 20. In another embodiment, the annular groove may instead be formedby a pin having an oblate spheroid shaped at its tip. The tip of the pinis forced into the hole 20 so that the tip sits within the hole. Thehole is deformed to have an annular groove as shown in FIG. 8A. Then themarker 25 is pressed into the hole 62 to take a similar shape as in FIG.8B.

E. Radiopaque Markers as Rivets

According to Concept E, a marker shaped as a rivet is used in place ofthe spherical marker 25. FIGS. 9A and 9B show respective side and topviews of the marker 27 shaped as a rivet. The head 28 may include theabluminal surface 27 a or luminal surface 27 b of the rivet 27. In thedrawings, the head 28 includes the abluminal surface 27 a. It may bepreferred to the have the head 28 be the luminal surface portion of therivet 27 for assembly purposes, since then the scaffold may be placedover a mandrel and the tail portion of the rivet deformed by a tool(e.g., a pin) applied externally to the scaffold abluminal surface. Therivet 27 has a head diameter d1 and the shank 27 c diameter d2 is aboutequal to the hole 22 diameter. The head 28 has a height of h2, which isabout the amount the head 28 will extend beyond the abluminal surface 22a of the strut portion 21 a. While not desirable, it may be anacceptable protrusion for a head 28 that does not extend more than about25 microns, or from about 5 to 10 microns up to about 25 microns fromthe abluminal surface 22 a, or a head that extends by an amount no morethan about 25% of the strut thickness. The same extent of protrusionbeyond the luminal surface 22 b may be tolerated for the deformed tailof the rivet.

Referring to FIG. 9C there is shown the rivet in the hole 22. Thedeformed tail 27 b′ secures the rivet 27 in the hole 22. The overallheight h1 is preferably not more than about 40% or about 10%-40% greaterthan the strut thickness (t) and the tail height is about the same as,or within 5 to 200 microns in dimension compared to the head height h2.

The rivet 27 may be attached to the hole 22 of the strut portion 21 a byfirst inserting the rivet 27 into the hole 22 from the bore side of thescaffold so that the head 28 rests on the luminal surface 22 b of thestrut portion 21 a. The scaffold is then slipped over a tight fittingmandrel. With the mandrel surface pressed against the head 28 a tool(e.g., a pin) is used to deform the tail 27 b to produce the deformedtail 27 b′ in FIG. 9C. In some embodiments, the rivet 27 may be firstinserted into the hole 22 from the abluminal side so that head 28 restson the abluminal surface 22 a of the strut potion 21 a. With the head 28held in place by a tool or flat surface applied against the abluminalsurface, the tail 27 b is deformed by a tool, pin, or mandrel which isinserted into the bore or threaded through the scaffold pattern from anadjacent position on the abluminal surface. In some embodiments therivet 27 may be a solid body (FIG. 9A-9B) or a hollow body, e.g., theshank is a hollow tube and the opening extends through the head 28 ofthe rivet.

In some embodiments a rivet is a hollow or solid cylindrical tube anddevoid of a pre-made head 28. In these embodiments the tube (solid orhollow) may be first fit within the hole then a pinch tool used to formthe head and tail portions of the rivet.

Referring to FIGS. 10A-10B and 11A-11B there is shown embodiments forsecuring a marker using a starting cylindrical tube hollow (tube 65) orsolid (tube 75), respectively.

Referring to FIGS. 10A-10B there is an attachment of a marker shaped asa hollow tube 65 placed into the strut portion 21 a hole and deformedusing a pinching tool 60. FIG. 10B shows the deformed marker 65′. Thetube 65 has an inside cylindrical surface 67 and outer diameter that isabout, or slightly greater than the hole 22 diameter. The tube has anundeformed length about equal to about 10%-40%, or 40%-80% greater thanthe strut thickness (t). The deformed tube/rivet has a deformed length(h2) of about 10-50% greater than the strut thickness and/or anundeformed length (h3) of about 15% to 70% greater than the strutthickness (t).

The pinching tool 60 includes an upper arm 60 a and lower arm 60 b. Thedeforming faces of the two arms 60 a, 60 b are the same. The faceincludes a deforming face 62 a, 62 b respectively shaped as anapex,point, hemisphere or convex surface, so that when pressed into thetube the end portions extending above the strut surface 22 a, 22 brespectively will be pushed outwardly, as shown in FIG. 10B. The arm'sflattening surface 63 a, 63 b flattens the material against the strutsurface. As can be appreciated from the drawings the deformed ends 65a′, 65 b′ of the deformed tube 65′ resemble the faces of the deformingfaces 63 a, 63 b.

Referring to FIGS. 11A-11B there is an attachment of a marker shaped asa solid tube 75 placed into the strut portion 21 a hole and deformedusing a pinching tool 70. FIG. 11B shows the deformed marker 75′. Thetube has an undeformed length about equal to about 10%-40%, or 40%-80%greater than the strut thickness (t). The deformed tube/rivet has adeformed length (h2) of about 10-50% greater than the strut thicknessand/or an undeformed length (h3) of about 15% to 70% greater than thestrut thickness (t).

The pinching tool 70 includes an upper arm 70 a and lower arm 70 b. Thedeforming faces of the two arms 70 a, 70 b are the same. The facesinclude a deforming face 72 a for arm 70 a and deforming face 72 b forarm 70 b, both of which may be shaped with an apex, point, hemisphere,or convex surface, so that when pressed into the tube the end portionsextending above the strut surface 22 a, 22 b respectively will be pushedoutwardly, as shown in FIG. 11B. The arm's flattening surface 73 a, 73 bflattens the material against the strut surface. As can be appreciatedfrom the drawings the deformed ends 75 a′, 75 b′ of the deformed tube75′ resemble the faces of the deforming faces 73 a, 72 a, 73 b, and 73a.

F. Use of a Polygonal or Irregular Marker Shape

According to Concept F, an irregular-shaped marker having protrudingedges is placed in a lased hole prior to a thermal process that shrinksthe lased hole. Polymeric bioresorbable scaffolds may be laser cut froma tube. This thin wall, precision tubing can be fabricated by extrusionand expansion processes that include stretch blow molding. The tubingresulting from such processes is formed by deformation of the polymer,which can result in residual stresses remaining in the tube. Heating thetube above its glass transition temperature (Tg) releases these stressesand can be used advantageously to shrink features such as lased markerbead holes to increase securement of a previously placed radiopaquemarker. In an alternative embodiment, the temperature of the scaffold israised above the Tg of the tube material and the marker placed into thesofter, heated polymer. This allows the polymer to become morecompliant, or flow and thus allow a marker, particularly an irregularlyshaped marker, to interact with the polymer surfaces to a greaterdegree, thereby raising the frictional forces and/or forming amechanical fit, depending on the marker type used.

Referring to FIG. 12A and 12B there is shown an irregularly shapedmarker 85 placed in the hole 22 of the strut portion 21 a. The hole 22may be at ambient temperature or at an elevated temperature (about 0-20Degrees C above the Tg of the strut material). Alternately, the hole 22is heated above the Tg after the marker is inserted. The marker 85 hasbumps, edges, corners or burrs 81 over its surface that when placed inthe hole 22 deforms the hole, as illustrated in FIG. 12B. The engagementbetween the marker 85 and hole may form a mechanical interlock. For amarker with cylindrical symmetry, a degree of roughness can be definedas the maximum and minimum distances in terms of radius from the markerscylindrical axis (e.g., difference between inner and out diameter as amaximum degree of roughness, or % of inner or outer diameter). For themarker 85 this distance from max to min may be between 5 to 50% of themaximum marker diameter The marker may have a flower, star or polygonalshape to produce the same effect. When placed in the hole 22 the hole 22deforms. The marker 85 may or may not deform, depending on thetemperature of hole 22 and the hardness of the marker material.

G. Snap-In Marker

According to Concept G, a snap-in marker is used. Referring to FIGS. 13Aand 13B there is shown a marker 95 having a preformed head 98 and tail92. The shank 95 c of the marker has an extent about equal to that thehole 22, which in this case is a diameter. The length of the shank isabout, slightly less, or slightly more than the strut thickness. Inother embodiments the marker 95 may be rectangular, hexagonal orpolygonal for fitting into the holes shown in FIGS. 4A, 5A, 6A or 6C.The distance between abluminal surface 95 a and luminal surface 95 b inFIG. 13B satisfies inequality IE.2 or IE.4, defined below.

Platinum, and especially platinum/iridium alloys, are stronger thanpolymeric materials because they are metals. Many assembly andsecurement process use snap-fit parts where the tolerances and shapesare designed to hold parts together without fasteners. The main featureof the marker 95 is the head 98 and tail 92 having an enlarged diameterover the shank 95 c part. There could be formed on portions 98 and 92round ridges, or more wedge shaped features. When pressed in, thepolymer will deform preferentially allowing the tail 92 or head 98 topass through, or imbed within the hole to become partially or fullyrecessed within the hole 22. When the tail 92 or head 98 passescompletely through hole 22, the polymer surface 22 a or 22 b will snapunder marker feature 98 or 92, securing it and preventing movement ineither direction.

With respect to any of Concepts A through G, the marker material may beplatinum, platinum/iridium alloy, iridium, tantalum, palladium,tungsten, niobium, zirconium, or alloys thereof. The marker material mayalso be of biodegradable metals such as iron, zinc, magnesium, manganeseor their alloys.

For some embodiments included under Concept A (e.g., the embodimentsshown in FIGS. 3A-3C); some embodiments included under Concept E (e.g.,the embodiments shown in FIGS. 9A-9C, 10A-10B and 11A-11B); and someembodiments included under Concept G (e.g., the embodiments shown inFIGS. 13A-13B) the following inequalities IE.1-IE.4 apply:

t×(1.2)≤L≤t×(1.8) or 1.2≤(L/t)≤1.8   IE.1

t×(1.1)≤L′≤t×(1.5) or 1.1≤(L′/t)≤1.5   IE.2

t×(1.0)≤L≤t×(1.8) or 1.0≤(L/t)≤1.8   IE.3

t×(1.0)≤L′≤t×(1.5) or 1.0≤(L′/t)≤1.5   IE.4

Where:

-   -   t is the average strut, bar arm or link thickness, or wall        thickness of the tube from which the scaffold was made. The        thickness t may vary between about 80 to 150 microns, 80 to 120        microns, 80 to 110 microns, 80 to 100 microns, or the thickness        may be about 100 microns, or the thickness may be up to 130 or        140 microns;    -   L is an undeformed length of the marker (Concept E); and    -   L′ is a deformed length of the marker (measured from the        abluminal surface portion to the luminal surface portion for        Concept E), length of the marker (Concept G), or distance        between abluminal and luminal surfaces of a coating and/or        polymer fill (Concept A).

Exemplary values for t are about 80 microns to 120 microns, or about 100microns and L′ or L being between about 100 microns and 150 microns.

The relations IE.1, IE.2, IE.3 and IE.4 reflect a need to maintain a lowprofile for struts exposed in the bloodstream, while ensuring the markerwill be securely held in the strut. The concern addressed here is thedegree thrombogenicity of the scaffold, which can be influenced by astrut thickness overall and/or protrusion from a strut surface. Bloodcompatibility, also known as hemocompatibility or thromboresistance, isa desired property for scaffolds and stents. The adverse event ofscaffold thrombosis, while a very low frequency event, carries with it ahigh incidence of morbidity and mortality. To mitigate the risk ofthrombosis, dual anti-platelet therapy is administered with all coronaryscaffold and stent implantation. This is to reduce thrombus formationdue to the procedure, vessel injury, and the implant itself. Scaffoldsand stents are foreign bodies and they all have some degree ofthrombogenicity. The thrombogenicity of a scaffold refers to itspropensity to form thrombus and this is due to several factors,including strut thickness, strut width, strut shape, total scaffoldsurface area, scaffold pattern, scaffold length, scaffold diameter,surface roughness and surface chemistry. Some of these factors areinterrelated. The effect of strut thickness on acute thrombogenicity hasbeen documented and studied both in vivo and in silico.

The above description of illustrated embodiments of the invention,including what is described in the Abstract, is not intended to beexhaustive or to limit the invention to the precise forms disclosed.While specific embodiments of, and examples for, the invention aredescribed herein for illustrative purposes, various modifications arepossible within the scope of the invention, as those skilled in therelevant art will recognize.

These modifications can be made to the invention in light of the abovedetailed description. The terms used in claims should not be construedto limit the invention to the specific embodiments disclosed in thespecification.

1. A method for making a medical device, comprising: providing a polymer scaffold including a strut having a hole formed in the strut, wherein the hole has a length, a width, and a hole opening located on a first side and a second side of the strut; and using a rivet comprising a radiopaque material and having a head and a shank, wherein a diameter of the head is greater than a diameter of the shank, the shank includes a tail and a medial portion, and the shank's medial portion is between the tail and the head; attaching the rivet to the scaffold including placing the shank into the hole; and deforming the tail, whereupon the deformed tail has a width that exceeds the hole width. 2-3. (canceled)
 4. The method of claim 1, wherein the first side and the second side are a luminal side and an abluminal side, respectively, of the hole opening, wherein the head is placed at the luminal side and held in place by a mandrel disposed within a bore of the scaffold, and the tail extends from the abluminal side of the hole opening, and the deforming step includes compressing the rivet between a roller or a pin applied to the tail at the abluminal side, and a surface of the mandrel applied to the head at the luminal side of the opening. 5-7. (canceled)
 8. The method of claim 1, wherein the marker has an undeformed length L measured from the head to the tail and before the deforming step, a deformed length L′ measured from the head to the deformed tail, the strut has a thickness t, and wherein the marker lengths L, L′ and strut thickness t are related as 1.2≤L/t≤1.8 and 1.1≤(L′/t)≤1.5.
 9. The method of claim 1, wherein the scaffold comprises a polymer having a glass transition temperature (TG), and the scaffold is heated 0-20 degrees above TG when the shank is placed in the hole.
 10. The method of claim 1, wherein the polymeric scaffold comprises a polymer having a glass transition temperature (TG), and the scaffold is heated 0-20 degrees above TG after the shank is placed in the hole.
 11. The method of claim 1, wherein the radiopaque material is platinum, platinum/iridium alloy, iridium, tantalum, palladium, tungsten, niobium, zirconium, iron, zinc, magnesium, or manganese, or their alloys. 12-20. (canceled)
 21. The method of claim 1, wherein the scaffold is made from a polymer comprising poly(L-lactide), wherein the scaffold has a wall thickness between 80 and 120 microns, and wherein following the deforming step a distance measured from the head to the deformed tail is between 100 microns and 150 microns.
 22. The method of claim 1, wherein the hole width is a diameter and the deformed tail width is a greater than the diameter of the hole.
 23. The method of claim 1, wherein the hole diameter is about the same as the shank diameter before the deforming step. 